The mission of the Mitochondrial Core of the Program Project is to provide the most advanced methods in mitochondrial analysis to use as dependent variables for testing the hypothesis that mitochondrial decline is a major component of the aging process. This will permit the characterization of changes in mitochondrial function in each of the genetic models proposed in the Program Project, including the mitochondrial DNA (mtDNA) mutations that result from structural gene mutations in mtDNA polymerase gamma (pol gamma). The mitochondria generate most of the energy of the cell by the process of oxidative phosphorylation. As a toxic by-product of oxidative phosphorylation, the mitochondria also generate most of the cellular reactive oxygen species (ROS) that damage cellular lipids, proteins and nucleic acids. Finally, a decline in mitochondrial energy output or an increase in mitochondrial oxidative stress can trigger apoptosis by activation of the mitochondrial permeability transition pore. Since mitochondrial function declines with age, resulting in increased ROS production, and cell loss from apoptosis is central to the aging processes, it follows logically that the mitochondria must also be central to the aging process. To facilitate the further clarification of the role of mitochondrial defects in aging, we propose to provide an integrated set of mitochondrial assays. These will include assessing the decline in energy production, accumulation of oxidative damage, stimulation of apoptosis, accumulation of mtDNA mutations, and alterations in the expression of mitochondrial genes encoded by the mitochondrial and nuclear DNA.